NASA Scientific and Technical Aerospace Reports

educators, researchers and professors who have engaged in breast cancer research led by the researchers from JHU, are guiding
the faculty through this development. The objectives of this training program are to allow the trainees the opportunity to
develop fundable research proposals, to conduct successful clinical research projects, and to publish and to train other WSSU
researchers. The faculty post docs will be able to apply their knowledge to assist minority elderly women to learn how to
discover signs of cancer before the cancer becomes hard to treat. The knowledge gained will allow these researchers to
participate in the training of other researchers in the area of breast cancer. Consistent with year 2 objectives, the faculty post
docs have attended several training activities, submitted research abstracts and grant applications, presented in scientific
conferences, and are designing the program for future WSSU researchers.
DTIC
Cancer; Clinical Medicine; Education; Females; Mammary Glands; Medical Science; Mortality
20040111693 Maryland Univ., Baltimore, MD
Novel MHC Class II Breast Cancer Vaccine Using RNA Interference (RNAi) to Down-Regulate Invariant Chain (Ii)
Thompson, James; May 2004; 28 pp.; In English; Original contains color illustrations
Contract(s)/Grant(s): DAMD17-03-1-0337
Report No.(s): AD-A425843; No Copyright; Avail: CASI; A03, Hardcopy
Our goal is to induce a strong CD4+ T cell response against tumor antigens by preferentially presenting endogenous tumor
antigens via class II major histocompatibility complex molecules (MHC II). MHC II can present endogenous tumor antigens
if expressed in the absence of Invariant chain (Ii). We have up-regulated MHCII and down regulated Ii without affecting MHC
II expression in tumor cells. Using the key transcription factor class II trans- activator (CIITA) we have coordinately
up-regulated all class II MHC molecules (DR, DP, DQ) and associated molecules such as the Invariant chain in a Human
mammary carcinoma (MCF10) . We have successfully down regulated the invariant chain in MCF10 cells, up regulated for
MHC II, using retroviral vectors that express siRNAs as hairpin loops. Immuno-fluorescence shows no down regulation of
MHC II molecules on the cell surface after Ii was down regulated. We will test the ability of our vaccine to present tumor
antigen by observing whether these cells can stimulate HER2/neu restricted CD4(+) or CD8(+)T cells. These tumor cells could
be used as a vaccine stimulating both CD4(+) and CD8(+)T cells in close proximity inducing a powerful long- term immune
response against tumor sharing common tumor antigen with the vaccine.
DTIC
Antigens; Cancer; Lymphocytes; Mammary Glands; Ribonucleic Acids; Vaccines
20040111694 Arkansas Univ., Little Rock, AR
Role of the Conserved Ologomeric Golgi Complex in the Abnormalities of Glycoprotein Processing in Breast Cancer
Cells
Zolov, Sergey N.; May 2004; 12 pp.; In English
Contract(s)/Grant(s): DAMD17-03-1-0243
Report No.(s): AD-A425847; No Copyright; Avail: CASI; A03, Hardcopy
The conserved oligomeric Golgi (COG) complex was identified as one of the evolutionary conserved protein complexes
that regulate a cis-Golgi step in intracellular vesicular transport. This evolutionary conserved complex is composed of eight
subunits. Mutations in the COG complex subunits result in defects in basic Golgi functions: glycosylation of secretory
proteins, protein sorting and retention of Golgi resident proteins. We propose that the COG3 protein plays one of the main roles
in these processes. We utilized RNA interference assay to knockdown COG3p in HeLa cells to determine the effect of its
depletion on Golgi proteins localization. siRNA dependent Cog3 depletion causes rapid Golgi fragmentation and possibly
accumulation of Golgi resident proteins in transport vesicles. Furthermore in COG3 depleted cells level of COG1, 2, 4 and
8 is also reduced while the level of COG5 and 6 subunits is not changed. We found that the COG complex physically interacts
with components of intra- Golgi trafficking machinery including v-SNARE GS28. COG3 protein is localized on Golgi in
normal conditions but in breast cancer cells in addition to the Golgi it is also found on peripheral structures where it is
colocalized with SNARE protein GS28. We concluded that mammalian COG complex serves as a ‘docking station’ for
retrograde intra-Golgi vesicles and that the lobe A of COG complex (subunits 1-4) is essential for this process. These results
help to further define the COG complex function in protein trafficking.
DTIC
Abnormalities; Cancer; Cells (Biology); Mammary Glands; Oligomers; Proteins
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